In vivo imaging of axonal degeneration and regeneration in the injured spinal cord

In vivo imaging of axonal degeneration and regeneration in the injured spinal cord
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DOI:
10.1038/nm1229
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发表时间:
2005-05-01
期刊:
影响因子:
82.9
通讯作者:
Misgeld, T
Misgeld, T
中科院分区:
医学1区
文献类型:
--
作者:
Kerschensteiner, M;Schwab, ME;Misgeld, T

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中央轴突对横断的不良反应是脊髓损伤后预后不佳的原因。在这里,我们在脊髓损伤后的几天内监测活转基因小鼠脊髓中的单个荧光轴突。我们发现,在创伤后30分钟内,轴突会后退数百微米。这种急性形式的轴突变性在机制上与更延迟的断开的远端轴突的沃勒氏变性相似,但急性变性对近端和远端轴突的影响相同。体内成像进一步显示,许多轴突在病变后6-24小时内尝试再生。这种生长反应虽然强劲,但似乎由于轴突无法在正确的方向上导航而失败。这些结果表明,脊髓损伤的延时成像可以为评估脊髓损伤的发病机制和评估促进再生的治疗方法提供强有力的分析工具。
The poor response of central axons to transection underlies the bleak prognosis following spinal cord injury. Here, we monitor individual fluorescent axons in the spinal cords of living transgenic mice over several days after spinal injury. We find that within 30 min after trauma, axons die back hundreds of micrometers. This acute form of axonal degeneration is similar in mechanism to the more delayed Wallerian degeneration of the disconnected distal axon, but acute degeneration affects the proximal and distal axon ends equally. In vivo imaging further shows that many axons attempt regeneration within 6-24 h after lesion. This growth response, although robust, seems to fail as a result of the inability of axons to navigate in the proper direction. These results suggest that time-lapse imaging of spinal cord injury may provide a powerful analytical tool for assessing the pathogenesis of spinal cord injury and for evaluating therapies that enhance regeneration.